The long term objective of this proposal is to establish reliable human tumor xenograft systems which will be used in the treatment of non- Hodgkin's lymphoma as well as other cancers. Commercial applications which would derive from such systems include: (i) improved screening of compounds for anti-tumor activities; (ii) evaluation of new cancer treatment modalities; (iii) optimizing combination therapies; and (iv) use in developing customized therapies to fit the individual patient. The specific aims of this Phase 1 proposal are to evaluate several parameters which are relevant to optimizing the ability of either human B-cell lines of primary tumor tissue (mainly non-Hodgkin's lymphomas) to become established and usable in SCID mice. Specifically, we propose to: (i) optimize the method of administering human B-cell lines are primary tumor cells to SCID mice; (ii) evaluate the ability of different lymphoma types and/or stages to engraft SCID mice; and (iii) manipulate the SCID mouse host to determine both the effect of the murine background genotypes as well as natural killer (NK) cell function on the ability of human tumor xenografts to become established in SCID mice.